Autonomic arousal detection system and method

ABSTRACT

Various approaches to detecting arousals from sleep involve generating signals modulated by muscle tone, brainwave activity, and/or other nervous system activity associated with a patient&#39;s autonomic arousal response. Generating the signals and/or detecting autonomic arousals from sleep may be performed using an implantable device. Arousal information may be useful to identify sleep disorder events associated with arousals from sleep, for diagnostic purposes, and/or for therapy adjustment.

RELATED PATENT DOCUMENTS

This application is a continuation of U.S. patent application Ser. No.10/920,675, filed Aug. 17, 2004, now U.S. Pat. No. 8,606,356, whichclaims the benefit of Provisional Patent Application Ser. No.60/504,344, filed on Sep. 18, 2003, to which priority is claimedpursuant to 35 U.S.C. §119(e) and which is hereby incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates generally to methods and systems fordetection of arousals from sleep.

BACKGROUND OF THE INVENTION

Sleep is generally beneficial and restorative to a patient, exertinggreat influence on the quality of life. The human sleep/wake cyclegenerally conforms to a circadian rhythm that is regulated by abiological clock. Regular periods of sleep enable the body and mind torejuvenate and rebuild. The body may perform various tasks during sleep,such as organizing long term memory, integrating new information, andrenewing tissue and other body structures.

Lack of sleep and/or decreased sleep quality may be have a number ofcausal factors including, e.g., nerve or muscle disorders, respiratorydisturbances, and emotional conditions, such as depression and anxiety.Chronic, long-term sleep-related disorders e.g., chronic insomnia,sleep-disordered breathing, and sleep movement disorders, includingrestless leg syndrome (RLS), periodic limb movement disorder (PLMD) andbruxism, may significantly affect a patient's sleep quality and qualityof life.

Movement disorders such as restless leg syndrome (RLS), and a relatedcondition, denoted periodic limb movement disorder (PLMD), are emergingas one of the more common sleep disorders, especially among olderpatients. Restless leg syndrome is a disorder causing unpleasantcrawling, prickling, or tingling sensations in the legs and feet and anurge to move them for relief. RLS leads to constant leg movement duringthe day and insomnia or fragmented sleep at night. Severe RLS is mostcommon in elderly people, although symptoms may develop at any age. Insome cases, it may be linked to other conditions such as anemia,pregnancy, or diabetes.

Many RLS patients also have periodic limb movement disorder (PLMD), adisorder that causes repetitive jerking movements of the limbs,especially the legs. These movements occur approximately every 20 to 40seconds and cause repeated arousals and severely fragmented sleep.

A significant percentage of patients between 30 and 60 years experiencesome symptoms of disordered breathing, primarily during periods ofsleep. Sleep disordered breathing is associated with excessive daytimesleepiness, systemic hypertension, increased risk of stroke, angina andmyocardial infarction. Disturbed respiration can be particularly seriousfor patients concurrently suffering from cardiovascular deficiencies.Disordered breathing is particularly prevalent among congestive heartfailure patients, and may contribute to the progression of heartfailure.

Sleep apnea is a fairly common breathing disorder characterized byperiods of interrupted breathing experienced during sleep. Sleep apneais typically classified based on its etiology. One type of sleep apnea,denoted obstructive sleep apnea, occurs when the patient's airway isobstructed by the collapse of soft tissue in the rear of the throat.Central sleep apnea is caused by a derangement of the central nervoussystem control of respiration. The patient ceases to breathe whencontrol signals from the brain to the respiratory muscles are absent orinterrupted. Mixed apnea is a combination of the central and obstructiveapnea types. Regardless of the type of apnea, people experiencing anapnea event stop breathing for a period of time. The cessation ofbreathing may occur repeatedly during sleep, sometimes hundreds of timesa night and occasionally for a minute or longer.

In addition to apnea, other types of disordered respiration have beenidentified, including, for example, hypopnea (shallow breathing),dyspnea (labored breathing), hyperpnea (deep breathing), and tachypnea(rapid breathing). Combinations of the disordered respiratory eventsdescribed above have also been observed. For example, Cheyne-Stokesrespiration (CSR) is associated with rhythmic increases and decreases intidal volume caused by alternating periods of hyperpnea followed byapnea and/or hypopnea. The breathing interruptions of CSR may beassociated with central apnea, or may be obstructive in nature. CSR isfrequently observed in patients with congestive heart failure (CHF) andis associated with an increased risk of accelerated CHF progression.

An adequate duration and quality of sleep is required to maintainphysiological homeostasis. Untreated, sleep disturbances may have anumber of adverse health and quality of life consequences ranging fromhigh blood pressure and other cardiovascular disorders to cognitiveimpairment, headaches, degradation of social and work-relatedactivities, and increased risk of automobile and other accidents.

SUMMARY OF THE INVENTION

The present invention is directed to systems and methods for detectingarousals of a patient during sleep. One embodiment of the invention isdirected to a method for acquiring sleep information including autonomicarousal events. The method involves sensing one or more physiologicalconditions modulated by a patient's autonomic arousal response.Autonomic arousal events occurring during sleep are detected based onthe one or more sensed signals. At least one of sensing thephysiological signals and detecting the autonomic arousal events isperformed at least in part implantably.

Another embodiment of the invention is directed to a method foracquiring sleep-related information. An arousal signal modulated bychanges in muscle tone associated with autonomic arousal is sensed usinga sensor disposed on an implantable therapy device. Autonomic arousalevents are detected based on the arousal signal.

Yet a further embodiment of the invention involves a method fordetecting arousals from sleep. One or both of a signal modulated bybrainwave activity associated with an autonomic arousal response and asignal modulated by changes in muscle tone associated with the autonomicarousal response are generated. Autonomic arousal events are detected,using an implantable device, based on at least one of the brainwavesignal and the muscle tone signal.

Another embodiment of the invention involves a system for detectingautonomic arousal events. The system includes an implantable therapydevice and one or more sensors mechanically coupled to the implantabletherapy device. The sensors are configured to sense one or morephysiological conditions modulated by a patient's autonomic arousalresponse. An arousal detector is coupled to the sensor and is configuredto detect autonomic arousal events based on the sensed physiologicalconditions.

In accordance with another embodiment of the invention, a system detectsautonomic arousal events occurring during sleep. The system includes oneor more sensors configured to sense one or more physiological conditionsassociated with a patient's autonomic arousal response. An implantablearousal detector is coupled to the one or more sensors. The arousaldetector is configured to detect autonomic arousal events based on theone or more physiological conditions.

One embodiment of the invention is directed to a medical systemdetecting autonomic arousal events occurring during sleep. The systemincludes one or more sensors configured to sense one or morephysiological conditions associated with a patient's autonomic arousalresponse. The system also includes an implantable arousal detectorcoupled to the one or more sensors. The arousal detector is configuredto detect autonomic arousal events based on the one or morephysiological conditions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1D are a block diagrams of systems that may be used toimplement arousal detection in accordance with embodiments of thepresent invention;

FIG. 1E illustrates graphs of signals from an electroencephalogram (EEG)sensor and an electromyogram (EMG) sensor used for arousal detection inaccordance with embodiments of the present invention;

FIGS. 1F-1I are diagrams illustrating various configurations of anarousal sensor coupled to an implanted medical device in accordance withembodiments of the present invention;

FIG. 2 is a graph of a normal respiration signal measured by atransthoracic impedance sensor that may be utilized in accordance withembodiments of the present invention;

FIG. 3A depicts a flow diagram illustrating various optional processesthat may be implemented in connection with arousal detection accordingto embodiments of the invention;

FIG. 3B is a flow chart illustrating a sleep detection method based onsignals from an accelerometer and a minute ventilation sensor inaccordance with embodiments of the present invention;

FIG. 4 is a graph of an accelerometer signal indicating patient activitylevel that may be used for sleep detection and arousal in accordancewith embodiments of the present invention;

FIG. 5 is a graph of a patient's heart rate and sensor indicated ratethat may be used for sleep detection and arousal in accordance with anembodiment of the present invention;

FIG. 6 is a graph of baseline trending for a minute ventilation (MV)signal used for sleep detection in accordance with embodiments of thepresent invention;

FIG. 7 illustrates adjustment of an accelerometer sleep threshold usingan MV signal in accordance with embodiments of the present invention

FIG. 8 is a respiration signal graph illustrating respiration intervalsused for disordered breathing detection according to embodiments of thepresent invention;

FIG. 9 is a graph of a respiration signal illustrating various intervalsthat may be used for detection of apnea in accordance with embodimentsof the present invention;

FIG. 10 is a respiration graph illustrating abnormally shallowrespiration utilized in detection of disordered breathing in accordancewith embodiments of the present invention;

FIG. 11 is a flow chart illustrating a method of apnea and/or hypopneadetection according to embodiments of the present invention;

FIG. 12 illustrates a medical system including an implantable cardiacrhythm management device that cooperates with a patient-externalrespiration therapy device to provide coordinated patient monitoring,diagnosis and/or therapy in accordance with an embodiment of the presentinvention;

FIG. 13 is an illustration of an implantable cardiac device including alead assembly shown implanted in a sectional view of a heart, the deviceused in connection with arousal detection in accordance with embodimentsof the present invention;

FIG. 14 is an illustration of a thorax having an implanted subcutaneousmedical device that may be used in connection with arousal detection inaccordance with an embodiment of the present invention; and

FIG. 15 is a block diagram of a cardiac rhythm management (CRM) systemsuitable for implementing an arousal detection methodology in accordancewith embodiments of the present invention.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the present invention as defined by theappended claims.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings, which form a part hereof, and inwhich are shown by way of illustration, various embodiments by which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the present invention.

An adequate quality and quantity of sleep is required to maintainphysiological homeostasis. Prolonged sleep deprivation or periods ofhighly fragmented sleep ultimately will have serious healthconsequences. Chronic fragmented sleep may be associated with variouscardiac or respiratory disorders affecting a patient's health andquality of life.

Assessment of sleep is traditionally performed in a polysomnographicsleep study at a dedicated sleep facility. Polysomnographic studiesinvolve acquiring sleep-related data, including the patient's typicalsleep patterns and the physiological, environmental, contextual,emotional, and other conditions affecting the patient during sleep.However, such studies are costly, inconvenient to the patient, and maynot accurately represent the patient's typical sleep behavior. Sleepassessment in a laboratory setting presents a number of obstacles inacquiring an accurate picture of a patient's typical sleep patternsincluding arousals and sleep disorders. For example, spending a night ina sleep laboratory typically causes a patient to experience a conditionknown as “first night syndrome,” involving disrupted sleep during thefirst few nights in an unfamiliar location. In addition, sleeping whileinstrumented and observed may not result in a realistic perspective ofthe patient's normal sleep patterns.

Various aspects of sleep quality, including number and severity ofarousals, number and severity of autonomic arousal events, sleepdisordered breathing episodes, nocturnal limb movements, and cardiac,respiratory, muscle, and nervous system functioning may provideimportant information for diagnosis and/or therapy delivery.Superficially, sleep may viewed as a monolithic event that ischaracterized by a period of unconsciousness. If examined in greaterdetail, sleep periods may be described as involving a series of eventsor stages. For example, sleep is typically divided into various stagesof sleep, including rapid eye movement (REM) sleep and non-REM (NREM)sleep. Non-REM sleep may be further subdivided into stage 1, stage 2 andstage 3 non-REM sleep, for example.

One indicator of sleep quality is the number of arousals experiencedduring sleep. An arousal is an event that occurs during sleep and may beidentified based on changes in electroencephalogram (EEG) signals duringnon-REM sleep and changes in EEG and electromyogram (EMG) signals duringREM sleep. Arousal events may or may not culminate in wakefulness. Thepatient may experience an arousal event during sleep and never wake up.

In one implementation, arousal from sleep has been identified, forexample, based on a shift in the patient's EEG signal to a higherfrequency for a specified period of time during non-REM sleep assumingsleep has been previously detected. Arousals during REM sleep have beenidentified by the EEG arousal defined above in addition to changes in anEMG signal or body movements. Arousals, as identified based on changesin EEG signals, encompass activation of the patient's autonomic nervoussystem.

Activation of the patient's autonomic nervous system during sleep may beused to identify arousal events referred to herein as an autonomicarousal event. Autonomic arousal events may be identified by anautonomic arousal response involving transient activation of thepatient's autonomic nervous system. The autonomic arousal response mayor may not result in detectable changes to the patient's EEG signal.

Autonomic arousal events comprise transient changes during sleep thataffect autonomic physiological parameters such as heart rate, bloodpressure, cardiac output, peripheral vasoconstriction, sympathetic nervetraffic, and arteriole size, among other conditions. For example, anautonomic arousal event may be detected based on a change of about 4 mmHg increase in systolic blood pressure and/or about a 4 beat per minuteincrease in heart rate. As previously mentioned, autonomic arousalevents begin during sleep and may or may not result in wakefulness.Thus, the patient may experience a number of autonomic arousal eventswhile asleep without achieving a waking state. Nevertheless, theseautonomic arousal events disrupt the patient's sleep and degrade sleepquality.

Information about the autonomic arousal events may be stored in memory,and/or transmitted to a separate device for printing or display.Information about the autonomic arousal events may be used to diagnosesleep disorders and/or adjust patient therapy, such as cardiacstimulation therapy, drug therapy, neural stimulation therapy, and/orrespiration therapy. Trending sleep information including autonomicarousal events and correlating the sleep information with sleep disorderevents may be helpful in determining and maintaining appropriatetherapies for patients suffering from a range of sleep disorders.

Many sleep disorder events, e.g., disordered breathing events andmovement disorder events, are followed by autonomic arousal events.These autonomic arousals disrupt the normal sleep pattern and may beinvolved in causing chronic hypertension. The autonomic arousal responsemay be visible on signals generated by electroencephalogram (EEG)sensors, electromyogram (EMG) sensors, and/or other sensors sensitive toautonomic nervous system changes.

In accordance with embodiments of the present invention, informationrelated to the patient's autonomic arousal response may be collectedand/or analyzed. The identification of autonomic arousal events may beused for a variety of purposes, including detecting and/or verifyingsleep disorder events, trending the number of arousals per night, anddeveloping various indices such as an arousal index and/or a compositeindex based on arousals and sleep disorder events. The arousalinformation may be collected and used in the evaluation of sleep and/orsleep disorders.

Frequent arousals are indicative of a number of medical disorders,including sleep disorder such as nocturnal periodic limb movementsyndrome and/or sleep disordered breathing. Further, frequent arousalsof the sympathetic nervous system may lead to chronic hypertension orother medical problems. The ability to detect individual and/oraggregate arousals may be used in diagnosing various medical disorders,including disordered breathing, movement disorders, and hypertension,for example.

If the patient receives therapy to treat a diagnosed medical disorder,then the ability to count and trend arousals also provides informationregarding therapy efficacy. For example, if arousals decline aftertherapy is delivered, then it may be assumed that the therapy providesan effective treatment for the diagnosed medical disorder. Further,detection of an arousal following delivery of therapy may be used toprovide feedback for therapy control.

The methodologies described herein involve using arousal information incombination with disordered breathing information. For example, thesystem may provide the capability of discriminating between disorderedbreathing events that cause arousals and disordered breathing eventsthat do not cause arousals. The detection of arousals may allow trendingof arousals that occur during sleep. The disordered breathing eventsthat are followed by arousals are considered to be the most disruptive,because repeated arousals prevent the patient from receiving a restfulsleep. Some patients continue to experience disordered breathing eventsduring an aroused status. It may be desirable to ignore disorderedbreathing events that occur during an aroused state. The ability todetect an arousal and ignore subsequently detected disordered breathingevents during arousal may improve the accuracy of disordered breathingindices, e.g., apnea/hypopnea index.

FIGS. 1A through 1C illustrate embodiments of the invention directed todetection arousal from sleep. As depicted in FIG. 1A, an arousaldetection system may comprise, for example, a sensor 105 that generatesa signal modulated by changes in muscle tone associated with autonomicarousal. Such a signal may be generated, for example, using anelectromyogram sensor or a strain gauge positioned in contact with ornear skeletal muscle, such as the pectoral muscle. The sensor 105 isdisposed on an implantable device 150, such as an implantable cardiacrhythm management system (pacemaker, defibrillator, cardiac monitor,cardiac resynchronizer), implantable drug pump, implantable neuralstimulator, or other implantable diagnostic or therapeutic device. Theimplantable device 150 may implantably monitor various physiologicalconditions and deliver therapy to the patient. For example, theimplantable device may deliver cardiac stimulation therapy, neuralstimulation therapy, drug therapy, and/or other therapies orcombinations of therapies to treat various diseases or disordersaffecting the patient. In some embodiments, the implantable devicedelivers therapy to treat sleep disorders, for example. Implantablyperforming an operation comprises performing the operation using acomponent, device, or system that is partially or fully implanted withinthe body.

The sensor 105 may be positioned on the housing, header, lead system, orother component of the implantable device 150 so that the sensor 105 isin contact with, or near, skeletal muscle. The sensor 105 generatessignals modulated by changes in muscle tone associated with autonomicarousal from sleep. The sensor 105 is communicatively coupled to anarousal detector 120. The sensor 105 and the arousal detector 120 maycommunicate through a wired or wireless communication link, for example.The arousal detector 120 detects arousals from sleep based on the signalgenerated by the sensor 105.

FIG. 1B illustrates another embodiment of the invention. A sensor system110 may comprise one or both of a muscle tone sensor e.g., an EMGsensor, configured to generate a signal modulated with changes in muscletone associated with autonomic arousals and a brainwave sensor, e.g., anEEG sensor, configured to generate a signal modulated by brainwaveactivity associated with autonomic arousals. The EMG sensor generatessignals modulated by changes in muscle tone associated with autonomicarousals from sleep. The EEG sensor generates a signal modulated bybrainwave activity associated with autonomic arousals from sleep. TheEMG and EEG sensors are communicatively coupled to an arousal detector120 disposed within a housing of an implantable device 140. The arousaldetector 120 detects arousals from sleep based on at least one of theEEG signal and the EMG signal.

Other sensors may be used in connection with arousal detection. Forexample, an accelerometer may be employed to detect patient movementcorrelated to arousal. An electrogram or other cardiac sensor may beused to detect various cardiac parameters associated with arousal. Forexample, heart rate increases upon arousal, the AV delay decreases uponarousal, and heart rate variability is modified by autonomic tonechanges associated with arousal. Cardiac output increases duringarousal, as may be measured via an impedance sensor. Blood pressure,measured, for example, by a lead-based pressure gauge, is modulated byarousal and may be utilized in arousal detection. Peripheral arterialtonography may be used in arousal detection. Arteriole size, which maybe measured by photoplethysmography, decreases upon arousal due tosympathetic nervous system activation. Sympathetic nerve trafficmodulated by arousal may be sensed using microelectrodes coupled to animplantable device.

The implantable device 150 may monitor various physiological conditionsand/or deliver therapy to the patient. For example, the implantabledevice may deliver cardiac stimulation therapy, neural stimulationtherapy, drug therapy, or other therapies or combinations of therapiesto treat diseases or disorders affecting the patient. The implantabledevice may deliver therapy to treat sleep disorders, for example.

The block diagram of FIG. 1C depicts another embodiment of a system thatmay be used to detect arousals from sleep. The system includes adetector 115 configured to detect changes in the patient's nervoussystem. The changes may comprise sympathetic and/or parasympatheticnervous system changes. The system also includes an arousal detector inan implantable device, the arousal detector configured to detectarousals from sleep based on the nervous system changes. The system maybe configured to detect the presence of individual arousal events, thepresence of aggregate arousals, or the presence of both individual andaggregate arousals.

For example, in one implementation, the sensors may sense conditionsthat are modulated contemporaneously with an arousal event. In thisimplementation, the system may detect an individual arousal event duringor slightly after the occurrence of the arousal event, for example. Inanother implementation, the sensors may be sensitive to conditions thatare modulated by the aggregate effect of multiple arousal events thatoccur over a period of time. In such an implementation, detection ofindividual arousals may or may not occur. The implantable device 130 maydetect changes in physiological conditions that are caused by theoccurrence of multiple arousals. The changes in the physiologicalconditions are used by the system to determine that multiple arousalevents that have occurred over a period of time. A representative set ofconditions indicative of the occurrence of multiple arousal events overa period of time may include, heart rate variability, blood pressure,AV-delay, arteriole size, sympathetic nerve activity, among others. Thislist is not exhaustive and other conditions may be sensed by the systemto determine the occurrence of multiple arousal events.

FIG. 1D illustrates an embodiment of the present invention involvingdetection of arousals during sleep periods. The processes and systemsexemplified by these embodiments may be implemented alone or incombination with one or more processes and systems exemplified by otherembodiments described herein to provide a coordinated approach topatient monitoring, diagnosis, and/or therapy.

As is illustrated in FIG. 1D, a system 160, in accordance with anembodiment of the present invention, may include one or morepatient-internal and/or patient-external sensors 170 for sensing theautonomic arousal response of the patient. In one configuration, one ormore EMG sensors may be used. In other configurations, one or more EEGsensors, a combination of one or more EMG sensors and one or more EEGsensors, and/or one or more other types of sensors capable of sensingarousal may be employed.

If EMG sensors are employed, the sensors are positioned on or nearmuscles and used to sense muscle electrical signals (myopotentials)associated with the autonomic arousal response. In one example, the EMGsensors are placed on the header, housing, or lead system of animplanted device. For example, the EMG sensors may be placed on thehousing of a cardiac device capable that is capable of sensing cardiacactivity and/or delivering electrical stimulation to the heart. Thecardiac device housing may be implanted in the pectoral region. In thisimplementation, the EMG sensors are positioned to detect arousals basedon the electrical activity of the pectoral muscle.

Alternatively, or additionally, the system 160 may include, for example,one or more EEG sensors used to detect brain activity. The EEG sensorsmay be positioned on a respiratory mask assembly such as on therespiratory mask and/or respiratory mask strap of a CPAP device, forexample, or may be positioned appropriately to detect brain activity.Signals from the one or more sensors 170 may be transmitted to anarousal detector 162 located in an implantable device 161 via leads or awireless communication link, for example.

The implanted medical device 161 may perform one or a combination ofmonitoring, diagnostic, and/or therapeutic functions. Arousalinformation may be stored in the memory of a monitoring/diagnostic unit167 of the implanted medical device 161. The monitoring/diagnostic unit167 may include a processor for making evaluating the arousalinformation and/or determining values or indices using the arousalinformation. For example, the monitoring/diagnostic unit processor maydetermine the number of arousals occurring within a sleep period, orother specified time period. The monitoring/diagnostic unit processormay determine an arousal index (arousals detected per unit time), anapnea/hypopnea index (apneas or hypopneas detected per unit time), orother indices. Further, the monitoring/diagnostic unit processor mayevaluate the sleep disorder events to determine if arousals areassociated with the sleep disorder events. For example, if an arousal isdetected within a predetermined time period after a sleep disorder eventis detected, the arousal may be associated with the sleep disorderevent. Using this process, arousals from sleep that are associated withsleep disorder events can be discriminated from arousals from sleep thatare not associated with sleep disorder events.

The arousal information may be processed, trended, displayed, and/ortransmitted to another device, such as an advanced patient management(APM) system 180 or a programmer 190, periodically or on command.Advanced patient management systems involve a system of medical devicesthat are accessible through various communications technologies,including wireless and wired communication links. Patient data may bedownloaded from one or more of the medical devices periodically or oncommand, and stored at the patient information server. The physicianand/or the patient may communicate with the medical devices and thepatient information server, for example, to provide or acquire patientdata or to initiate, terminate or modify therapy.

The data stored on the patient information server may be accessible bythe patient and the patient's physician through one or more terminals,e.g., remote computers located in the patient's home or the physician'soffice. The patient information server may be used to communicate to oneor more of the patient-internal and patient-external medical devices toprovide remote control of the monitoring, diagnosis, and/or therapyfunctions of the medical devices.

In one embodiment, the patient's physician may access and evaluatepatient data transmitted from the medical devices to the patientinformation server. After evaluation of the patient data, the patient'sphysician may communicate with one or more of the patient-internal orpatient-external devices through the APM system to initiate, terminate,or modify the monitoring, diagnostic, and/or therapy functions of thepatient-internal and/or patient-external medical systems. Systems andmethods involving advanced patient management techniques are furtherdescribed in U.S. Pat. Nos. 6,336,903, 6,312,378, 6,270,457, and6,398,728, hereby incorporated herein by reference.

In one application, for example, the number of arousals may be countedand used to calculate an arousal index to quantify the number ofarousals experienced by the patient per unit time. Arousal informationmay be used to determine a number of sleep quality indices. Variousapproaches for sleep quality assessment that may be utilized inconnection with embodiments of the invention, such as the implementationof various sleep quality indices, are described in commonly owned U.S.patent application Ser. No. 10/642,998, filed Aug. 18, 2003, now U.S.Pat. No. 8,002,553, and incorporated herein by reference.

Autonomic arousal represents a sleep stage that may be detected by theapproaches described herein. Arousal detection may be utilized inconnection with determining sleep stage and information about varioussleep stages experienced by the patient. Various processes for acquiringinformation about sleep stages, some of which may be used in connectionwith embodiments described herein, are described in commonly owned U.S.patent application Ser. No. 10/643,006, filed Aug. 18, 2003, now U.S.Pat. No. 8,192,376, and incorporated herein by reference.

The arousal information may be used in diagnosing and treating a varietyof disorders, including nocturnal sleep disorders, such as periodic legmovement disorder, sleep disordered breathing, such as sleep apnea,hypertension, and other conditions. The ability to count and trend thesearousals provides diagnostic information regarding patient status withrespect to the disorders. For example, autonomic arousals are associatedwith causing hypertension. A presence of hypertension may be determinedor predicted based on arousal information, such as a trend of arousalevents over time. Trending arousals may be used to improve therapy usedto treat sleep disorders.

Arousals fracture sleep staging, leading to disrupted sleep, and as aconsequence, daytime sleepiness. An arousal will bring a patient out ofREM sleep or deep sleep (stage 3-4), and bring them temporarily to awaking state. As a consequence, the amount of REM and deep sleep islimited, since the patient has to go back through Stage 1-2 sleep beforethey enter REM or deep sleep.

The implanted device 161 may include a sleep detector 176 and one ormore sleep sensors 166 for determining the onset and/or offset of sleep.The sleep detector 176 may determine the sleep state of the patientusing one or more patient conditions related to sleep, such as activitylevel, time of day, heart rate, respiration rate, posture, proximity tobed, and/or other factors indicative of sleep. Sleep detection mayinvolve, for example, sensing sleep-related conditions and comparing thesensed sleep-related conditions to thresholds. The patient's sleep statemay be determined based on the comparison. In one embodiment describedbelow, sleep detection involves comparing a first sleep-relatedparameter to a threshold that is modulated by a second sleep-relatedparameter. Automatic sleep detection facilitates calculation of variousindices used to assess sleep quality such as number of arousals persleep period, and/or other indices based on sleep period, for example.

In one configuration, arousal information may be used by a therapycontrol unit 175 within the implantable device 161 for initiating,terminating, or adjusting therapy. Alternatively, the arousalinformation may be transmitted to the APM system 180 or other remotedevice for automatic or physician conducted analysis. The APM system 180may transmit control signals to the implanted device 161 to initiate,terminate or modify therapy delivered by the implanted device 161. Forexample, arousal feedback information may be used by an APM system, animplantable cardiac device, an external respiration therapy device, orother therapy device or combinations of devices to provide closed-loopcontrol of the therapy using arousal information feedback.

In one configuration, the arousal detector 162 is a component of theimplanted device 161 and is positioned within the implanted devicehousing, for example. The arousal detection function may alternativelybe performed in a patient-internal or patient-external device other thanthe implanted device 161, such as an APM system 180, for example. Inthis configuration, sensor data collected by the implanted device 161from the sensors 170 may be transmitted to the APM system 180 and usedfor arousal detection.

Detection of arousals involves evaluating the arousal informationacquired from the sensors 170 for a characteristic signature ofautonomic arousal. Autonomic arousal responses, as detected using EEGsensors and EMG sensors, are illustrated in the graph of FIG. 1B.

Referring now to FIG. 1E, a sleep study sensor array output isillustrated including an apnea event terminating in an arousal. Arousaldetection may be implemented using implantable sensors capable ofdetecting changes in the sympathetic or parasympathetic nervous system.These changes may be either short-term (i.e., changes associated withindividual arousals) or long-term (i.e., aggregate effect of multiplearousals). A short-term effect of arousal includes, for example, theactivation of sympathetic nerve activities. Sympathetic orparasympathetic changes, or the changes of autonomic balance can beassessed, for example, by heart rate variability (HRV), which can bedetected using a device configured to sense cardiac activity, changes inheart rate, and/or changes in AV conduction.

In the graphs of FIG. 1E, the abscissa of all the graphs is the sametime period during the sleep analysis of a patient. The ordinate of eachof the graphs is the signal amplitude of the respective sensor. Traces181, 182, 183, and 184 are the top, second, third, and fourth tracesrespectively, plotted from sensors adapted to produceelectroencephalogram (EEG) signals. Evident in all four traces, butparticularly pointed out in traces 181 and 182 is a characteristicsignature of an EEG signal indicative of arousal 194. A trace 185provides an electrocardiogram (EKG) of the heart beats during the timeperiod of the graph. A trace 186 provides an electromyogram definingmuscular movement during the time period of the graph. Particularlyevident in the trace 186 is a characteristic signature of an EMG signalindicative of arousal 192.

Traces 187, 188, 191, and 189 illustrate various parameters related torespiration. Trace 187 is nasal pressure, 188 is thoracic effort, 191 isabdominal effort, and 189 is the sum of the thoracic and abdominaleffort. Trace 193 depicts the blood oxygen saturation level of thepatient. Pulmonary activity may be sensed through the use of internalsensors, such as impedance sensors and/or minute ventilation sensorsdescribed further below.

In accordance with aspects of the present invention, arousal detectionmay be used in connection with detection of sleep disorders, such asdisordered breathing. Sleep disorders, such as disordered breathingand/or PLMD may cause the patient to arouse from sleep frequently duringa sleep period. Thus arousals from sleep follow the sleep disorderevent. In one configuration, arousal detection may be used as asurrogate for direct detection of the disordered condition. For example,in systems that do not have a respiration sensor capable of detectingdisrupted respiration, arousal detection may be used as a surrogate fordetecting disrupted respiration. In systems that do not have a sensorcapable of detecting nocturnal limb movements, arousal detection may beused as a surrogate for detecting PLMD, or other movement disorders.

In one implementation, arousal detection may be combined with sleepdisorder event detection to verify the occurrences of sleep disorders.Referring again to FIG. 1D, the system 160 may include sleep disorderevent detector 6015 for sensing patient conditions associated with sleepdisorders, e.g., sleep apnea and PLMD. In one configuration, the sleepdisorder sensor system 6015 includes a transthoracic impedance sensorcapable of sensing respiration. The respiration signals are evaluated bya sleep disorder event detector 164 to detect occurrences of disorderedbreathing. In another configuration, the sleep disorder sensor system6015 includes an accelerometer positioned on a limb of the patient tosense nocturnal movements. The accelerometer signals are evaluated bythe sleep disorder event detector 164 to detect occurrences of sleepmovement disorders.

Arousal information may be used by the sleep disorder event detector 164to augment detection of sleep disorder events. For example, arousalinformation may be used to confirm occurrences of disordered breathingas described earlier. Arousal information may be used to distinguishbetween correctly and incorrectly identified sleep disorder eventsindicated by the sleep disorder event detector 164.

Further, information from the arousal detector may be used to separatesleep disorder events, e.g., apnea, hypopnea and/or PLMD, followed byarousal versus those terminated without arousal. The sleep disorderevents that are followed by arousal are considered to be the mostdisruptive, as these arousals interrupt the normal course of sleep andprevent the patient from receiving a full sleep cycle each night.Detecting these types of sleep disorder events enhances the specificityof sleep disorder event detection and guides diagnosis and/or therapy.

The arousal information may be used to modify therapy for sleep disorderevents such as disordered breathing. In various implementations, thearousal information and/or disordered breathing information may be usedby a therapy control unit 175 in the implanted device 161 to modifydisordered breathing therapy delivered to the patient. The therapy maybe delivered by the implanted device, or by a separate, possiblyexternal, therapy device.

For example, electrical stimulation therapy may be provided by theimplanted device 161. Detection of disordered breathing may be used toinitiate the electrical stimulation therapy. Detection of arousal,indicating the end of the disordered breathing event, may be used toterminate the electrical stimulation therapy, for example.

In another example, electrical stimulation therapy may be provided, andthe number of arousals monitored. If the electrical stimulation therapycauses too many arousals, the electrical stimulation therapy may beadjusted or terminated.

In another example, the APM system 180 may receive information aboutsleep disorder events from the sleep disorder event detector 164 and/orarousal information from the arousal detector 162. The information maybe automatically evaluated by the APM system 180, or may be evaluated bythe patient's physician. The APM system 180 may be used to transmitcontrol signals to the therapy control unit 175 of the implanted device161 to initiate, terminate or modify the therapy delivered to thepatient.

In various configurations, an EMG sensor may be positioned on a housingor header of an implantable device, such as a cardiac rhythm managementdevice, or may be located on a catheter or lead coupled to the cardiacrhythm management device. An EMG sensor located on a device positionedin the pectoral region provides access to skeletal muscle that may beexploited to detect arousal.

FIGS. 1F-1I illustrate various configurations of an arousal sensormechanically coupled to an implanted medical device 121, such as animplantable pacemaker or implantable cardioverter/defibrillator inaccordance with embodiments of the invention. The implantable medicaldevice 121 may include a housing 122 enclosing the medical devicecircuitry and a header 124 for coupling a lead system 141 to thecircuitry of the medical device 121.

An arousal sensor may be implemented, for example, using anelectromyogram (EMG) electrode 126 or force responsive sensor 131positioned on the housing 122 of the medical device 121 as illustratedin FIGS. 1C and 1D, respectively. FIG. 1H illustrates an arousal sensor128 positioned on the header 124 of the medical device 121.Alternatively, an arousal sensor 142, e.g., EMG electrode or straingauge, may be positioned on the lead system 141 or may be coupled to thehousing 122 through a catheter or lead system 141, such as by using theheader 124, as illustrated in FIG. 1F.

FIG. 3A depicts a flow diagram illustrating various optional processesthat may be implemented in connection with arousal detection accordingto embodiments of the invention. Detection of sleep 320 may be used toinform the arousal detection process 310 and the sleep disorder eventdetection process 340. Information about sleep, sleep disorder events,and arousals from sleep are monitored 370. The information may be usedto diagnose sleep-related disorders and/or other disorders 375,calculate arousal and sleep disorder indices, develop trend information380, correlate arousals with sleep disorder events 385, and/or adjusttherapy delivered to the patient 390. Upon detection of a sleep disorderevent 340, e.g., sleep disordered breathing, therapy to mitigate thesleep disorder event may be initiated 350. Arousal detection 310 signalsthe end of the sleep disorder event, and therapy may be terminated 360following detection of arousal from sleep.

Various embodiments of the invention involve the use of arousaldetection cooperation with sleep detection. Various aspects of sleepquality, including number and severity of arousals, sleep disorderedbreathing episodes, nocturnal limb movements, correlation of sleepdisorder events to arousals, and other cardiac, respiratory, muscle, andnervous system functioning may provide important information fordiagnosis and/or therapy delivery. An initial step to sleep qualityevaluation is an accurate and reliable method for discriminating betweenperiods of sleep and periods of wakefulness. Various approaches to sleepdetection, some of which may be used in combination with embodiments ofthe invention presented herein, are described in commonly owned U.S.patent application Ser. No. 10/309,771, now U.S. Pat. No. 7,189,204,filed Dec. 4, 2002, and incorporated herein by reference.

The flowchart illustrated in FIG. 3B is one example of an algorithmicapproach to sleep detection that may be used in cooperation withdetection of arousal from sleep in accordance with embodiments of theinvention. In an exemplary methodology described below, detection ofsleep is based in part on patient respiration. FIG. 2 illustrates normalbreathing cycles. Respiration may be sensed, for example, by measuringthe patient's transthoracic impedance. Transthoracic impedance increaseswith respiratory inspiration 220 and decreases with respiratoryexpiration 210. The impedance signal 200 is also proportional to theamount of air inhaled. Referring now to FIG. 2, a tranthoracic impedancesignal 200 is illustrated. The impedance signal 200 may be developed,for example, using intracardiac impedance electrodes in combination witha CRM device.

The variations in impedance during respiration, identifiable as thepeak-to-peak variation of the impedance signal 200, may be used todetermine the respiration tidal volume. Tidal volume (TV) corresponds tothe volume of air moved in a breath. Minute ventilation (MV) may also bedetermined, corresponding to the amount of air moved in a one minute.

In the flow chart of FIG. 3B, an accelerometer and a minute ventilationsensor are used to develop the first and second signals associated withsleep. A preliminary accelerometer signal sleep threshold is determined312. For example, the preliminary sleep threshold may be determined fromclinical data taken from a group of subjects or historical data takenfrom the patient over a period of time.

The activity level of the patient is monitored using an accelerometer314 that may be incorporated into an implantable cardiac pacemaker asdescribed above. Alternatively, the accelerometer may be attachedexternally to the patient. The patient's minute ventilation (MV) signalis monitored 316. The MV signal may be acquired, for example, based onthe transthoracic impedance signal as described above using animplantable cardiac device. Other methods of determining the MV signalare also possible and are considered to be within the scope of thisinvention.

In this example, the accelerometer signal represents the sleep detectionsignal associated with the sleep threshold. The MV signal is thethreshold adjustment signal used to adjust the sleep threshold. Heartrate is monitored 318 in this example to provide a sleep confirmationsignal.

Threshold adjustment may be accomplished by using the patient's MVsignal status 322 to moderate the accelerometer sleep threshold. If thepatient's MV signal status 322 is low relative to an expected MV levelassociated with sleep, the accelerometer sleep threshold is increased324. Similarly, if the patient's MV signal status 322 is high relativeto an expected MV level associated with sleep, the accelerometer sleepthreshold is decreased 344. Thus, when the patient's MV level is high,less activity is required to make the determination that the patient issleeping. Conversely when the patient's MV level is relatively low, ahigher activity level may result in detection of sleep. The use of twosleep-related signals to determine a sleep condition enhances theaccuracy of sleep detection over previous methods using only onesleep-related signal to determine that a patient is sleeping.

Various signal processing techniques may be employed to process the rawsensor signals. For example, a moving average of a plurality of samplesof each sleep-related signal may be calculated and used as thesleep-related signal. Furthermore, the sleep-related signals may befiltered and/or digitized. If the MV signal status 322 is high relativeto an expected MV level associated with sleep, the accelerometer sleepthreshold is decreased 344. If the MV signal status 322 is low relativeto an expected MV level associated with sleep, the accelerometer sleepthreshold is increased 324.

If the sensed accelerometer signal is less than or equal to the adjustedsleep threshold, indicated by a yes at decision 326, and if the patientis not currently in a sleep state 328, then the patient's heart rate ischecked 334 to confirm the sleep condition. If the patient's heart rateis compatible with sleep 334, then sleep onset is determined 336. If thepatient's heart rate is incompatible with sleep, then the patient'ssleep-related signals continue to be monitored.

If the accelerometer signal is less than or equal to the adjusted sleepthreshold at decision 326, and if the patient is currently in a sleepstate 328, then a continuing sleep state 332 is determined and thepatient's sleep-related signals continue to be monitored for sleeptermination to occur.

If the accelerometer signal is greater than the adjusted sleepthreshold, as indicated by a no condition at decision 326, and thepatient is not currently in a sleep state 338, then the patient'ssleep-related signals continue to be monitored until sleep onset 336 isdetected. If the accelerometer signal is greater than the adjusted sleepthreshold at decision 326, and the patient is currently in a sleep state338, then sleep termination is detected 342.

The graphs of FIGS. 4-7 illustrate sensor data, trends, and theadjustment of the accelerometer sleep thresholds using the MV signal.The relationship between patient activity and the accelerometer and MVsignals is trended over a period of time to determine relative signallevels associated with a sleep condition. FIG. 4 illustrates an activitylevel 430 as indicated by an accelerometer signal 410 (the accelerometersignal 410 is represented in the graph legend as trace XL). Theaccelerometer signal 410 indicates a period of sleep 420 associated witha relatively low level of activity beginning at slightly before time23:00 and continuing through time 6:00. The accelerometer trends may beused to establish a threshold for sleep detection. The activity level430 may be derived, for example, by integrating the accelerometer signal410 within a moving time window, where the length of the time window isadjusted to compensate for movement during sleep or other spuriousactivity or inactivity sources.

The patient's heart rate for the same time period illustrated in FIG. 4is graphed in FIG. 5. A heart rate signal 510 appropriately tracks theactivity level 430 (FIG. 4) indicated by the accelerometer, indicating asimilar period 530 of low heart rate corresponding to sleep. A sensorindicated rate 520 is graphed in FIG. 5, and is represented in the graphlegend as trace SIR. As illustrated in FIG. 5, the sensor indicated rate520 may differ from the actual heart rate signal 510. For example, thesensor indicated rate 520 may be sensed from an implanted electrode orother sensor and correlates to the hemodynamic need of the patient.

FIG. 6 is a graph of baseline trending for an MV signal. Historical dataof minute ventilation of a patient is graphed over an 8 month period. InFIG. 6, a trace is provided for: one month as a trace 610; one monthplus one day as a trace 620; three months as a trace 630; three monthplus one day as a trace 640; five months as a trace 650; and eightmonths as a trace 660. The MV signal trending data is used to determinethe MV signal level associated with sleep. In this example, a compositeMV signal using the historical data indicates a roughly sinusoidal shapewith the relatively low MV levels occurring approximately during theperiod from about hours 21:00 through 8:00. The low MV levels areassociated with periods of sleep, particularly evident at about hours3:00 through 6:00 in the graphs of FIG. 6, having The MV signal levelassociated with sleep may be used to implement sleep thresholdadjustment as will be described further below and in association withFIG. 7.

FIG. 7 illustrates adjustment of the accelerometer sleep threshold usingthe MV signal. FIG. 7 is based on the graph of FIG. 4, including theactivity level 430 as indicated by the accelerometer signal 410 (again,represented in the graph legend as trace XL). An initial sleep threshold710 is established using the baseline accelerometer signal data acquiredas discussed above. If the patient's MV signal is low relative to anexpected MV level associated with sleep, the accelerometer sleepthreshold is increased to an increased sleep threshold 720. If thepatient's MV signal level is high relative to an expected MV levelassociated with sleep, the accelerometer sleep threshold is decreased toa decreased sleep threshold 730. When the patient's MV level is high,less activity detected by the accelerometer is required to make thedetermination that the patient is sleeping. However, if the patient's MVlevel is relatively low, a higher activity level may result in detectionof sleep. The use of two sleep-related signals to adjust a sleepthreshold for determining a sleep condition enhances the accuracy ofsleep detection.

Additional sleep-related signals may be sensed and used to improve thesleep detection mechanism described above. For example, a posture sensormay be used to detect the posture of the patient and used to confirmsleep. If the posture sensor indicates a vertical posture, then theposture sensor signal may be used to override a determination of sleepusing the sleep detection and threshold adjustment signals. Othersignals may also be used in connection with sleep determination orconfirmation, including the representative set of sleep-related signalsassociated with sleep indicated above.

Various embodiments of the invention involve the use of arousaldetection cooperation with detection of sleep disorder events. In someimplementations presented herein, arousal detection is used incooperation with detection of sleep disordered breathing. Methods andsystems for detecting disordered breathing, aspects of which may beutilized in connection with the embodiments presented herein, aredescribed in commonly owned U.S. patent application Ser. No. 10/309,770,filed Dec. 4, 2002, now U.S. Pat. No. 7,252,640, and incorporated hereinby reference.

Episodes of disordered breathing may be determined, for example, usingthe tranthoracic impedance signal, and/or other information available tothe sleep disorder event detection circuitry. In one exemplaryimplementation, a disordered breathing event is declared when thepatient's tidal volume (TV) falls below a threshold. For example, whenthe TV, as indicated by the transthoracic impedance signal, falls belowa hypopnea threshold, then a hypopnea event is declared. In oneimplementation, a hypopnea event may be declared if the patient's tidalvolume falls below about 50% of a recent average tidal volume or otherbaseline tidal volume value. If the patient's tidal volume falls furtherto an apnea threshold, e.g., about 10% of the recent average tidalvolume or other baseline value, an apnea event is declared.

FIGS. 8-10 are graphs of transthoracic impedance, similar to FIG. 2previously described. FIG. 8 illustrates respiration intervals used fordisordered breathing detection useful in accordance with embodiments ofthe present invention. Detection of disordered breathing may involvedefining and examining a number of respiratory cycle intervals. Arespiration cycle is divided into an inspiration period 830corresponding to the patient inhaling, an expiration period 850,corresponding to the patient exhaling, and a non-breathing period 860occurring between inhaling and exhaling. Respiration intervals areestablished using an inspiration threshold 810 and an expirationthreshold 820. The inspiration threshold 810 marks the beginning of aninspiration period 830 and is determined by the transthoracic impedancesignal 200 rising above the inspiration threshold 810. The inspirationperiod 830 ends when the transthoracic impedance signal 200 is a maximum840.

The maximum transthoracic impedance signal 840 corresponds to both theend of the inspiration interval 830 and the beginning of an expirationinterval 850. The expiration interval 850 continues until thetransthoracic impedance 200 falls below an expiration threshold 820. Anon-breathing interval 860 starts from the end of the expiration period850 and continues until the beginning of a next inspiration period 870.

Detection of sleep apnea and severe sleep apnea is illustrated in FIG.9. The patient's respiration signals are monitored and the respirationcycles are defined according to an inspiration 930, an expiration 950,and a non-breathing 960 interval as described in connection with FIG. 8.A condition of sleep apnea is detected when a non-breathing period 960exceeds a first predetermined interval 990, denoted the sleep apneainterval. A condition of severe sleep apnea is detected when thenon-breathing period 960 exceeds a second predetermined interval 995,denoted the severe sleep apnea interval. For example, sleep apnea may bedetected when the non-breathing interval exceeds about 10 seconds, andsevere sleep apnea may be detected when the non-breathing intervalexceeds about 20 seconds.

Hypopnea is a condition of disordered breathing characterized byabnormally shallow breathing. FIG. 10 is a graph of tidal volume derivedfrom transthoracic impedance measurements. The graph of FIG. 10illustrating the tidal volume of a hypopnea episode may be compared tothe tidal volume of a normal breathing cycle illustrated previously inFIG. 2, which illustrated normal respiration tidal volume and rate. Asshown in FIG. 10, hypopnea involves a period of abnormally shallowrespiration.

Hypopnea is detected by comparing a patient's respiratory tidal volume1003 to a hypopnea tidal volume 1001. The tidal volume for eachrespiration cycle may be derived from transthoracic impedancemeasurements acquired in the manner described previously. The hypopneatidal volume threshold may be established by, for example, usingclinical results providing a representative tidal volume and duration ofhypopnea events. In one configuration, hypopnea is detected when anaverage of the patient's respiratory tidal volume taken over a selectedtime interval falls below the hypopnea tidal volume threshold.Furthermore, various combinations of hypopnea cycles, breath intervals,and non-breathing intervals may be used to detect hypopnea, where thenon-breathing intervals are determined as described above.

In FIG. 10, a hypopnea episode 1005 is identified when the average tidalvolume is significantly below the normal tidal volume. In the exampleillustrated in FIG. 10, the normal tidal volume during the breathingprocess is identified as the peak-to peak value identified as therespiratory tidal volume 1003. The hypopnea tidal volume during thehypopnea episode 1005 is identified as hypopnea tidal volume 1001. Forexample, the hypopnea tidal volume 1001 may be about 50% of therespiratory tidal volume 1003. The value 50% is used by way of exampleonly, and determination of thresholds for hypopnea events may bedetermined as any value appropriate for a given patient.

In the example above, if the tidal volume falls below about 50% of therespiratory tidal volume 1003, the breathing episode may be identifiedas a hypopnea event. The period of time that the patient's tidal volumeremains below about 50% of the respiratory tidal volume 1003 defines theperiod of the hypopnea event. FIG. 11 is a flow chart illustrating amethod of apnea and/or hypopnea detection useful in accordance withembodiments of the present invention. Various parameters are established1101 before analyzing the patient's respiration for disordered breathingepisodes, including, for example, inspiration and expiration thresholds,sleep apnea interval, severe sleep apnea interval, and hypopnea tidalvolume (TV) threshold.

The patient's transthoracic impedance is measured 1105 as described inmore detail above. If the transthoracic impedance exceeds 1110 theinspiration threshold, the beginning of an inspiration interval isdetected 1115. If the transthoracic impedance remains below 1110 theinspiration threshold, then the impedance signal is checked 1105periodically until inspiration 1115 occurs.

During the inspiration interval, the patient's transthoracic impedanceis monitored until a maximum value of the transthoracic impedance isdetected 1120. Detection of the maximum value signals an end of theinspiration period and a beginning of an expiration period 1135.

The expiration interval is characterized by decreasing transthoracicimpedance. When, at determination 1140, the transthoracic impedancefalls below the expiration threshold, a non-breathing interval isdetected 1155.

If the transthoracic impedance determination 1160 does not exceed theinspiration threshold within a first predetermined interval, denoted thesleep apnea interval 1165, then a condition of sleep apnea is detected1170. Severe sleep apnea 1180 is detected if the non-breathing periodextends beyond a second predetermined interval, denoted the severe sleepapnea interval 1175.

When the transthoracic impedance determination 1160 exceeds theinspiration threshold, the tidal volume from the peak-to-peaktransthoracic impedance is calculated, along with a moving average ofpast tidal volumes 1185. The peak-to-peak transthoracic impedanceprovides a value proportional to the tidal volume of the respirationcycle. This value is compared at determination 1190 to a hypopnea tidalvolume threshold. If, at determination 1190, the peak-to-peaktransthoracic impedance is consistent with the hypopnea tidal volumethreshold for a predetermined time 1192, then a hypopnea cycle 1195 isdetected.

In some exemplary implementations presented herein, arousal detection isused in cooperation with detection of nocturnal disordered movementevents. Restless leg movement syndrome and periodic limb movementdisorder are closely associated disorders also known as Myoclonus andEkbom Syndrome, respectively. Restless Leg Syndrome (RLS) and PeriodicLimb Movement Disorder (PLMD) affect 2-8% of the population in theUnited States. Both conditions are characterized by involuntarymovements of the limbs, most typically the legs.

Restless Leg Syndrome (RLS) is a disorder that occurs during periods ofwakefulness. Periodic Limb Movement Disorder (PLMD) occurs during sleepor in transitions from wake to sleep or sleep to wake. Patients with RLSor PLMD may suffer twitching, tingling, aching, burning, itching, orpulling sensations in their arms and/or legs. Because RLS patients mayalso suffer from sleep-related PLMD, these patients are often arousedfrom sleep, and their ability to return to sleep is delayed by RLS.

RLS patients are unable to sit still and may have to remain active torelieve limb discomfort. For patients suffering from RLS, relaxation andpassive activities become increasingly problematic, adversely affectingthe quality of life.

For both PLMD and RLS patients, sleep quality deteriorates. When apatient tries to fall asleep, the leg discomfort begins. In severecases, patients only sleep a few hours at night, resulting in excessivedaytime sleepiness and disruption of the normal daily routine. RLS andPLMD patients often complain of irritability, anxiety, and depression.The severity of RLS and/or PLMD ranges from infrequent minor discomfortto daily agony that leads some patients to contemplate suicide.

Symptoms of PLMD may come and go through the night and over the courseof one's life. PLMD episodes may last a few minutes or several hours.There may be an interval of days, weeks or months between episodes. PLMDpatients may experience sudden but rhythmic limb jerks occurringperiodically, e.g., every 20 to 40 seconds. PLMD episodes may be seenprimarily in the first third of the night, during non-REM sleep.Patients with RLS often have PLMD, but patients with PLMD do not alwayshave RLS. Polysomnographic studies indicate that about 70% to 90% ofpatients with RLS have PLMD.

PLMD movements may be characterized, for example, by periodic flexion ofone or both legs involving bending at the hip and knee with upwardbending of the foot and the great toe, resembling a flexion reflex. Anormal healthy person may have five of these movements per hour. Thediagnosis of PLMD is given when more than five movements per hour occur.

Both genders are affected, with a slightly higher incidence in women.These conditions are seen more commonly with advancing age. Theprevalence of PLMD or RLS is 2% of the population of ages less than 30,5% of ages 30 to 50, and 25% of ages 50-60. The highest prevalence isseen in age 65 or older, with 44% of the population affected. Whileusually diagnosed in older groups, these disorders may be traced tochildhood. Hyperactive, fidgeting children or youths often labeled with“growing pains” may actually be showing the early manifestations of PLMDand RLS.

In accordance with embodiments of the invention, nocturnal disorderedmovement events such as bruxism events and PLMD events, for example, maybe detected using a system that is fully or partially implantable. Withreference to FIG. 1D an implantable medical device, e.g., a CRM device,incorporates a sleep disorder event detector 164 that may include amovement disorder detector. One or more sleep disorder sensors 165,e.g., movement sensors may be coupled to the sleep disorder eventdetector 164 within the implantable device 161.

The sleep disorder sensors 165 may include any sensor or any combinationof sensors capable of detecting motion and/or muscle activity associatedwith motion. For example, the patient's movements may be detected usingone or more accelerometers, one or more EMG sensors, and/or acombination of one or more accelerometers and one or more EMG sensors.

In one embodiment, one or more movement sensors (e.g., accelerometersand/or sub-movement EMG sensors) are coupled to the patient atappropriate locations to detect movements of the extremities, e.g., limbmovements, or other movements. Signals from the sleep disorder sensors165 are received and processed by the sleep disorder event detector 164in the implantable device 161. The sleep disorder event detector 164 maycooperate with a memory in a monitoring unit 167 to store informationabout the detected movements. Movement information may be stored,trended, displayed, and/or transmitted to a separate device, such as anAPM system 180 or a programmer 190 for further operations.

In another embodiment, illustrated in FIG. 1D, one or more movementsensors 165 are coupled to a sleep disorder event detector 164 withinthe implantable device 161, as previously discussed. The implantabledevice 161 also includes a therapy unit 175 that receives movementinformation from the sleep disorder event detector 164, the arousaldetector 162, and/or other components of the implantable device 161. Thetherapy unit may provide therapy, e.g., drug therapy, for variousmovement disorders such as RLS and/or PLMD.

In one example, the movement sensors 165 may include one of more EMGsensors placed on or in the anterior tibialis. Typical EMG bursts due toPLMD movements may last between 0.5-5 seconds and may recur every 20-40seconds, for example. The sleep disorder event detector 164 may detectPLMD if at least about 40 EMG bursts are detected within an 8 hour sleepperiod, for example. Sleep disruption caused by the PLMD movements maybe determined by any or a combination of the sleep detection techniquesdescribed herein, including, for example, electrical muscle activity(EMG) sensing, brain wave (EEG) sensing and/or a combination ofrespiration (MV) and activity sensing, among others. Movement disorderinformation may be downloaded to a programmer 190, an APM system 180, orother therapeutic or diagnostic device.

Arousal detection with or without sleep disorder event detection may beused in connection with delivering therapy to the patient. In oneimplementation, detection of an excessive number of arousals may triggertherapy adjustments that promote more restful sleep. Some examples oftherapies that may be used to treat patients with sleep disorders areoutlined below.

Drug therapy has been used to treat movement disorders and sleepdisordered breathing. Disordered breathing may also be treated usingoral appliances, electrical stimulation, respiration therapy, andsurgery, for example. Obstructive apnea is caused by an obstruction inthe patient's airway. Obstructive apnea has been associated withprolapse of the tongue and the surrounding structure into the pharynxduring sleep, thus occluding the respiratory pathway. Central apnea is aneurological disorder causing a derangement of the respiratory drivesignals, typically without any mechanical obstruction or otherventilatory defects. A commonly prescribed treatment for bothobstructive and central apneas is positive airway pressure. Positive airpressure devices deliver air pressure to the patient, often through afacial or nasal mask worn by the patient. In the case of obstructiveapnea, the application of a positive airway pressure keeps the patient'sthroat open, reducing the occlusion causing the apnea.

Prolapse of the tongue muscles has been attributed to diminishingneuromuscular activity of the upper airway. A treatment for obstructivesleep apnea involves compensating for the decreased muscle activity byelectrical activation of the tongue muscles. The hypoglossal (HG) nerveinnervates the protrusor and retractor tongue muscles. An appropriatelyapplied electrical stimulation to the hypoglossal nerve, for example,may prevent backward movement of the tongue, thus preventing the tonguefrom obstructing the airway.

Central sleep apnea may also be treated by phrenic nerve pacing, alsoreferred to as diaphragmatic pacing. Phrenic nerve pacing uses anelectrode implanted in the chest to stimulate the phrenic nerve. Thephrenic nerve is generally known as the motor nerve of the diaphragm. Itruns through the thorax, along the heart, and then to the diaphragm.Diaphragmatic pacing is the use of electronic stimulation of the phrenicnerve to control the patient's diaphragm and induce a respiratory cycle.Pacing the phrenic nerve may be accomplished by surgically placing anerve cuff on the phrenic nerve, and then delivering an electricstimulus. The electric stimulus of the phrenic nerve then causes thediaphragm to induce a respiratory cycle.

Recently, cardiac electrical stimulation therapy has been used as atherapy for disordered breathing. Cardiac electrical stimulation istypically implemented using an implanted electrical pulse generatorcoupled to endocardiac leads inserted into one or more heart chambers.

Cardiac electrical stimulation therapy may involve pacing one or morechambers of the heart. Pacing therapy may involve, for example, pacingone or more atria and/or one or more ventricles. In one implementation,overdrive pacing is used to mitigate disordered breathing.

Therapy for disordered breathing may involve non-excitatory electricalstimulation of one or more heart chambers, e.g., the left and/or rightventricles, or other cardiac sites. Non-excitatory electricalstimulation may be delivered during absolute refractory periods of thecardiac tissue, for example, to improve cardiac contractility. Thenon-excitatory stimulation therapy may be used alone or in combinationwith pacing therapy to provide a comprehensive therapy regimen forpatients with CHF and disordered breathing such as Cheyne-Stokesrespiration.

Some patients may benefit from a therapy regimen that includes acombination of the therapy techniques outlined above. For example,disordered breathing therapy may involve a combination of cardiacelectrical stimulation therapy and external respiration therapy.

In the example illustrated in FIG. 12, a mechanical respiration therapydevice 1220 providing positive airway pressure therapy cooperates withan implantable cardiac device, e.g., cardiac rhythm management system(CRM) device 1210 providing cardiac electrical stimulation therapy.Positive airway pressure devices may be used to deliver a variety ofrespiration therapies, including, for example, continuous positiveairway pressure (CPAP), bi-level positive airway pressure (bi-levelPAP), proportional positive airway pressure (PPAP), auto-titratingpositive airway pressure, ventilation, gas or oxygen therapies. Alltypes of positive airway pressure devices are referred to genericallyherein as xPAP devices.

A typical CPAP device delivers air pressure through a nasal mask worn bythe patient. The application of continuous positive airway pressurekeeps the patient's throat open, reducing or eliminating the obstructioncausing apnea. Positive airway pressure devices may be used to provide avariety of respiration therapies, including, for example, continuouspositive airway pressure (CPAP), bi-level positive airway pressure(bi-level PAP), proportional positive airway pressure (PPAP),auto-titrating positive airway pressure, ventilation, gas or oxygentherapies. Some positive airway pressure devices may also be configuredto provide both positive and negative pressure, such that negativepressure is selectively used (and de-activated) when necessary, such aswhen treating Cheyne-Stokes breathing, for example. The term xPAP willbe used herein as a generic term for any device using forms of positiveairway pressure (and negative pressure when necessary), whethercontinuous or otherwise.

The xPAP device 1220 develops a positive air pressure that is deliveredto the patient's airway through a tube system 1252 and a mask assembly1254 connected to the xPAP device 1220. The mask assembly 1254 mayinclude EEG sensors, such as one or more EEG sensors 1256 attached to astrap 1257 that is placed around the head of the patient, orelectrocardiogram (ECG) sensors attached to the mask or strap. In oneconfiguration, for example, the positive airway pressure provided by thexPAP device 1220 acts as a pneumatic splint keeping the patient's airwayopen and reducing the severity and/or number of occurrences ofdisordered breathing due to airway obstruction.

The CRM 1210 may deliver cardiac electrical stimulation therapy fordisordered breathing and/or for cardiac dysfunctions such asbradycardia, tachycardia and congestive heart failure. The CRM device1210 may include a number of sensors, such as cardiac sense electrodes,transthoracic impedance sensors, and/or patient activity sensors thatmay be used in connection with arousal detection, disordered breathingdetection, sleep detection and/or sleep disorder event detection. In oneembodiment, an arousal sensor e.g., an EMG sensor 1211, is positioned onthe housing of the CRM device 1210.

The CRM 1210 and xPAP 1220 devices may communicate directly through awireless communications link, for example. Alternatively, oradditionally, the CRM 1210 and xPAP 1220 devices may communicate withand/or through an APM device such as an APM system 1230, as will bedescribed further below. The CRM 1210 may include a lead system havingelectrodes for electrically coupling to the heart, for example.

In the embodiment depicted in FIG. 12, the EMG sensor 1211 and/or theEEG sensor 1256 may communicate with an arousal detector that may behoused within the CRM device 1210 or within the xPAP device 1220, forexample. The arousal detector detects arousals from sleep based onsignals from one or both of the EEG sensor 1256 and the EMG sensor 1211.Information about the detected arousals from sleep may be communicatedto the CRM 1210 and/or the xPAP 1220. The arousal information may beused to initiate, terminate or adjust the cardiac electrical stimulationand/or respiration therapy delivered to the patient.

Although FIG. 12 illustrates a CRM device 1210 used with a xPAP device1220 to provide coordinated patient monitoring, diagnosis and/ortherapy, any number of patient-internal and patient-external medicaldevices may be included in a medical system in accordance with thepresent invention. For example, a drug delivery device, such as a drugpump or controllable nebulizer, may be included in the system 1200. Thedrug delivery device may cooperate with either or both of the CRM device1210 and the xPAP device 1220 and may contribute to the patientmonitoring, diagnosis, and/or therapeutic functions of the medicalsystem 1200.

FIG. 13 is a partial view of an implantable device that may includecircuitry for autonomic arousal detection in accordance with embodimentsof the invention. In this example, an arousal detector 1335 isconfigured as a component of a pulse generator 1305 of a cardiac rhythmmanagement (CRM) device 1300. The implantable pulse generator 1305 iselectrically and physically coupled to an intracardiac lead system 1310.The arousal detector 1335 may alternatively be implemented in a varietyof implantable monitoring, diagnostic, and/or therapeutic devices, suchas an implantable cardiac monitoring device, an implantable drugdelivery device, or an implantable neurostimulation device, for example.

Portions of the intracardiac lead system 1310 are inserted into thepatient's heart 1390. The intracardiac lead system 1310 includes one ormore electrodes configured to sense electrical cardiac activity of theheart, deliver electrical stimulation to the heart, sense the patient'stransthoracic impedance, and/or sense other physiological parameters,e.g., cardiac chamber pressure or temperature. Portions of the housing1301 of the pulse generator 1305 may optionally serve as a canelectrode.

Communications circuitry is disposed within the housing 1301,facilitating communication between the pulse generator 1305 includingthe arousal detector 1335 and an external device, such as a sleepdisordered breathing therapy device and/or APM system. Thecommunications circuitry can also facilitate unidirectional orbidirectional communication with one or more implanted, external,cutaneous, or subcutaneous physiologic or non-physiologic sensors,patient-input devices and/or information systems.

The pulse generator 1305 may optionally incorporate a EMG sensor 1320disposed on the housing 1301 of the pulse generator 1305. The EMG sensormay be configured, for example, to sense myopotentials of the patient'sskeletal muscle in the pectoral region. Myopotential sensing may be usedin connection with arousal detection as described in more detail herein.

The pulse generator 1305 may further include a sensor configured todetect patient motion. The motion detector may be implemented as anaccelerometer positioned in or on the housing 1301 of the pulsegenerator 1305. If the motion detector is implemented as anaccelerometer, the motion detector may also provide acousticinformation, e.g. rales, coughing, S1-S4 heart sounds, cardiac murmurs,and other acoustic information.

The lead system 1310 of the CRM device 1300 may incorporate atransthoracic impedance sensor that may be used to acquire the patient'scardiac output, or other physiological conditions related to thepatient's autonomic arousal response. The transthoracic impedance sensormay include, for example, one or more intracardiac electrodes 1341,1342, 1351-1355, 1363 positioned in one or more chambers of the heart1390. The intracardiac electrodes 1341, 1342, 1351-1355, 1361, 1363 maybe coupled to impedance drive/sense circuitry 1330 positioned within thehousing of the pulse generator 1305.

The impedance signal may also be used to detect the patient'srespiration waveform and/or other physiological changes produce a changein impedance, including pulmonary edema, heart size, cardiac pumpfunction, etc. The respiratory and/or pacemaker therapy may be alteredon the basis of the patient's heart condition as sensed by impedance.

In one example, the transthoracic impedance may be used to detect thepatient's respiratory waveform. A voltage signal developed at theimpedance sense electrode 1352, illustrated in FIG. 2, is proportionalto the patient's transthoracic impedance and represents the patient'srespiration waveform. The transthoracic impedance increases duringrespiratory inspiration and decreases during respiratory expiration. Thetransthoracic impedance may be used to determine the amount of air movedin one breath, denoted the tidal volume and/or the amount of air movedper minute, denoted the minute ventilation. A normal “at rest”respiration pattern, e.g., during non-REM sleep, includes regular,rhythmic inspiration-expiration cycles without substantialinterruptions, as indicated in FIG. 2.

Returning to FIG. 13, the lead system 1310 may include one or morecardiac pace/sense electrodes 1351-1355 positioned in, on, or about oneor more heart chambers for sensing electrical signals from the patient'sheart 1390 and/or delivering pacing pulses to the heart 1390. Theintracardiac sense/pace electrodes 1351-1355, such as those illustratedin FIG. 13, may be used to sense and/or pace one or more chambers of theheart, including the left ventricle, the right ventricle, the leftatrium and/or the right atrium. The lead system 1310 may include one ormore defibrillation electrodes 1341, 1342 for deliveringdefibrillation/cardioversion shocks to the heart.

The pulse generator 1305 may include circuitry for detecting cardiacarrhythmias and/or for controlling pacing or defibrillation therapy inthe form of electrical stimulation pulses or shocks delivered to theheart through the lead system 1310. Arousal detection circuitry 1335 maybe housed within the housing 1301 of the pulse generator 1305. Thearousal detection circuitry 1335 may be coupled to various sensors,including the transthoracic impedance sensor 1330, EMG sensor 1320, EEGsensors, cardiac electrogram sensors, nerve activity sensors, and/orother sensors capable of sensing physiological signals modulated by thepatient's autonomic arousal response.

The arousal detector 1335 may be coupled to a sleep disorder detectorconfigured to detect sleep disorders such as disordered breathing,and/or movement disorders. The arousal detector and the sleep disorderdetector may be coupled to a processor that may use information from thearousal detector and the sleep disorder detector to associate sleepdisorder events with arousal events. The processor may trend the arousalevents, associate the sleep disorder events with arousal events, and/oruse the detection of the arousal events and/or the sleep disorder eventsfor a variety of diagnostic purposes. The sleep disorder detector and/orthe processor may also be configured as a component of the pulsegenerator 1305 and may be positioned within the pulse generator housing1301. In one embodiment, information about the arousal events and/or thesleep disorder events may be used to adjust therapy delivered by the CRMdevice 1300 and/or other therapy device.

In addition to the EMG sensor, the cardiac sensors and the impedancesensor described above, various other sensors, including, for example,EEG sensors, accelerometers, posture sensors, proximity sensors,electrooculogram (EOG) sensors, photoplethymography sensors, bloodpressure sensors, peripheral arterial tonography sensors, and/or othersensors useful in detecting autonomic arousal events and/or sleepdisorder events may also be coupled to the CRM device 1300.

FIG. 14 is a diagram illustrating an implantable transthoracic cardiacdevice that may be used in connection with detection of arousals fromsleep in accordance with embodiments of the invention. The implantabledevice illustrated in FIG. 14 is an implantable transthoracic cardiacsensing and/or stimulation (ITCS) device that may be implanted under theskin in the chest region of a patient. The ITCS device may, for example,be implanted subcutaneously such that all or selected elements of thedevice are positioned on the patient's front, back, side, or other bodylocations suitable for sensing cardiac activity and delivering cardiacstimulation therapy. It is understood that elements of the ITCS devicemay be located at several different body locations, such as in thechest, abdominal, or subclavian region with electrode elementsrespectively positioned at different regions near, around, in, or on theheart.

In accordance with one embodiment, an arousal sensor may be positionedon housing 1402, lead assembly 1406, or subcutaneous electrode assembly1407 of the ITCS device. An arousal detector may be positioned withinthe primary housing of the ITCS device. The primary housing (e.g., theactive or non-active can) of the ITCS device, for example, may beconfigured for positioning outside of the rib cage at an intercostal orsubcostal location, within the abdomen, or in the upper chest region(e.g., subclavian location, such as above the third rib). In oneimplementation, one or more electrodes may be located on the primaryhousing and/or at other locations about, but not in direct contact withthe heart, great vessel or coronary vasculature.

In another implementation, one or more electrodes may be located indirect contact with the heart, great vessel or coronary vasculature,such as via one or more leads implanted by use of conventionaltransvenous delivery approaches. In another implementation, for example,one or more subcutaneous electrode subsystems or electrode arrays may beused to sense cardiac activity and deliver cardiac stimulation energy inan ITCS device configuration employing an active can or a configurationemploying a non-active can. Electrodes may be situated at anteriorand/or posterior locations relative to the heart.

In the configuration shown in FIG. 14, a subcutaneous electrode assembly1407 can be positioned under the skin in the chest region and situateddistal from the housing 1402. The subcutaneous and, if applicable,housing electrode(s) can be positioned about the heart at variouslocations and orientations, such as at various anterior and/or posteriorlocations relative to the heart. The subcutaneous electrode assembly1407 is coupled to circuitry within the housing 1402 via a lead assembly1406. One or more conductors (e.g., coils or cables) are provided withinthe lead assembly 1406 and electrically couple the subcutaneouselectrode assembly 1407 with circuitry in the housing 1402. One or moresense, sense/pace or defibrillation electrodes can be situated on theelongated structure of the electrode support, the housing 1402, and/orthe distal electrode assembly (shown as subcutaneous electrode assembly1407 in the configuration shown in FIG. 14).

It is noted that the electrode and the lead assemblies 1407, 1406 can beconfigured to assume a variety of shapes. For example, the lead assembly1406 can have a wedge, chevron, flattened oval, or a ribbon shape, andthe subcutaneous electrode assembly 1407 can comprise a number of spacedelectrodes, such as an array or band of electrodes. Moreover, two ormore subcutaneous electrode assemblies 1407 can be mounted to multipleelectrode support assemblies 1406 to achieve a desired spacedrelationship amongst subcutaneous electrode assemblies 1407.

In particular configurations, the ITCS device may perform functionstraditionally performed by cardiac rhythm management devices, such asproviding various cardiac monitoring, pacing and/orcardioversion/defibrillation functions. Exemplary pacemaker circuitry,structures and functionality, aspects of which can be incorporated in anITCS device of a type that may benefit from multi-parameter sensingconfigurations, are disclosed in commonly owned U.S. Pat. Nos.4,562,841; 5,284,136; 5,376,476; 5,036,849; 5,540,727; 5,836,987;6,044,298; and 6,055,454, which are hereby incorporated herein byreference in their respective entireties. It is understood that ITCSdevice configurations can provide for non-physiologic pacing support inaddition to, or to the exclusion of, bradycardia and/or anti-tachycardiapacing therapies. Exemplary cardiac monitoring circuitry, structures andfunctionality, aspects of which can be incorporated in an ITCS of thepresent invention, are disclosed in commonly owned U.S. Pat. Nos.5,313,953; 5,388,578; and 5,411,031, which are hereby incorporatedherein by reference in their respective entireties.

An ITCS device can incorporate circuitry, structures and functionalityof the subcutaneous implantable medical devices disclosed in commonlyowned U.S. Pat. Nos. 5,203,348; 5,230,337; 5,360,442; 5,366,496;5,397,342; 5,391,200; 5,545,202; 5,603,732; and 5,916,243 and commonlyowned U.S. patent application Ser. No. 10/820,642 filed Apr. 8, 2004,now U.S. Pat. No. 7,570,997, and U.S. patent application Ser. No.10/821,248, filed Apr. 8, 2004, published as U.S. Published PatentApplication No. 2004-0215240, now abandoned, which are incorporatedherein by reference.

The housing of the ITCS device may incorporate components of a arousaldetection system including one or more of arousal detection circuitry,sleep detection circuitry, sleep disorder event detection circuitry,monitoring unit, for example as described in connection with FIG. 1D.

In one implementation, the ITCS device may include an impedance sensorconfigured to sense the patient's transthoracic impedance. The impedancesensor may include the impedance drive/sense circuitry incorporated withthe housing 1402 of the ITCS device and coupled to impedance electrodespositioned on the can or at other locations of the ITCS device, such ason the subcutaneous electrode assembly 1407 and/or lead assembly 1406.In one configuration, the impedance drive circuitry generates a currentthat flows between a subcutaneous impedance drive electrode 1409 and acan electrode on the primary housing 1402 of the ITCS device. Thevoltage at a subcutaneous impedance sense electrode 1408 relative to thecan electrode changes as the patient's transthoracic impedance changes.The voltage signal developed between the impedance sense electrode andthe can electrode is sensed by the impedance drive/sense circuitry.

Communications circuitry is disposed within the housing 1402 forfacilitating communication between the ITCS device and an externalcommunication device, such as a portable or bed-side communicationstation, patient-carried/worn communication station, externalprogrammer, APM system, or separate therapy device for example. Thecommunications circuitry can also facilitate unidirectional orbidirectional communication with one or more external, cutaneous, orsubcutaneous physiologic or non-physiologic sensors that may be used inconnection with arousal detection in accordance with embodiments of theinvention.

FIG. 15 is a block diagram of an arousal detection system that isimplemented in cooperation with a cardiac rhythm management (CRM) systemsuch as a pacemaker and/or cardioverter/defibrillator in accordance withan embodiment of the invention. The system may be completelyimplantable.

Cardiac sense circuitry 1560, cardiac therapy unit 1555, disorderedbreathing detector 1520, arousal detector, 1565, and sleep detector 1550are arranged within a housing that is hermetically sealed and suitablefor implanting within the patient, such as in the pectoral region of thepatient's chest. An accelerometer 1536, configured to detect patientactivity, may also be incorporated within the housing. An arousal sensor1535, e.g., an EMG sensor, is disposed on the housing so that the EMGsensor 1535 is positioned in contact with or near skeletal muscle, suchas the pectoral muscle. An intracardiac lead system includes cardiacelectrodes 1555 for electrically coupling to the patient's heart and oneor more transthoracic impedance electrodes for generating a respirationsignal.

The sleep detector uses the patient activity signal generated by theaccelerometer 1536 and the respiration signal generated by thetransthoracic impedance electrodes 1542 to determine if the patient isasleep or awake.

The disordered breathing detector detects disordered breathing eventsbased on the patient's respiration patterns, as described more fullyabove. The arousal detector compares the EMG signal to a characteristicarousal signature and detects arousal based on the comparison.Disordered breathing detection and arousal detection may be enhancedusing sleep/wake information provided by the sleep detector.

In one embodiment, the CRM provides cardiac electrical stimulation theto one or more heart chambers as therapy for disordered breathing.Various approaches to delivering cardiac electrical stimulation therapyfor treatment of disordered breathing, some of which may be utilizedconnection with embodiments presented herein, are described in commonlyowned U.S. patent application Ser. No. 10/643,203, filed Aug. 18, 2003,now U.S. Pat. No. 7,720,541 and incorporated herein by reference.

The therapy control unit 1555 may utilize signals from the sleepdetector 1550, disordered breathing detector 1520, and arousal detector1565 to initiate, terminate, and/or adjust the cardiac electricalstimulation therapy for disordered breathing. For example, the therapycontrol unit 1555 may initiate a process for treating disorderedbreathing episodes when the sleep detector 1550 determines that thepatient is asleep.

In one scenario, the therapy control unit 1555 may initiate cardiacelectrical stimulation, e.g., cardiac overdrive pacing, to treatdisordered breathing upon detection of a disordered breathing eventduring sleep. In another scenario, the therapy control unit 1555 mayinitiate cardiac electrical stimulation to treat disordered breathingwhen sleep is detected. The therapy control unit 1555 may adjust thecardiac electrical stimulation when a disordered breathing event isdetected during sleep. If an arousal is detected, then the therapycontrol unit 1555 may terminate or adjust the cardiac electricalstimulation therapy for disordered breathing. Adjustment of the cardiacelectrical stimulation therapy may involve increasing the pacing rate,initiating multi-site pacing, switching the cardiac pacing from one siteto another site. The pacing mode may be switched to a pacing mode thatpromotes atrial pacing, or promotes consistent ventricular pacing. Thepacing mode may be switched from single chamber to multiple chambers, orthe reverse. For example, a bi-ventricular mode may be switched to aleft ventricular mode only. Alternatively, a single chamber mode, e.g.,LV or RV, may be switched to a bi-ventricular mode. Other adjustmentsare also possible.

A number of the examples presented herein involve block diagramsillustrating functional blocks used for coordinated monitoring,diagnosis and/or therapy functions in accordance with embodiments of thepresent invention. It will be understood by those skilled in the artthat there exist many possible configurations in which these functionalblocks can be arranged and implemented. The functional blocks may beimplemented, for example, in hardware, software, or a combination ofhardware and software. The examples depicted herein provide examples ofpossible functional arrangements used to implement the approaches of thepresent invention.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will be apparent to those skilledin the art without departing from the invention. Accordingly, it isintended that the invention be limited only by the scope of the appendedclaims.

What is claimed is:
 1. A method for adjusting a patient neurostimulation therapy, comprising: sensing one or more physiological conditions modulated by a patient's autonomic arousal response; detecting autonomic arousal events occurring during sleep based on the one or more sensed physiological conditions, wherein at least one of sensing the physiological conditions and detecting the autonomic arousal events is performed at least in part implantably; discriminating between autonomic arousal events associated with sleep disorder events and autonomic arousal events not associated with sleep disorder events; and adjusting the patient neurostimulation therapy based, at least in part, on the discriminated autonomic arousal events.
 2. The method according to claim 1, wherein the patient therapy further comprises a cardiac stimulation therapy, and wherein the method further comprises adjusting the patient cardiac stimulation therapy based, at least in part, on the discriminated autonomic arousal events.
 3. The method according to claim 1, wherein the patient therapy further comprises a hypertension therapy, and wherein the method further comprises adjusting the patient hypertension therapy based, at least in part, on the discriminated autonomic arousal events.
 4. The method according to claim 1, wherein only autonomic arousal events not associated with sleep disorder events are used in adjusting the neurostimulation therapy.
 5. The method of claim 1 wherein the autonomic arousal events are detected by observing an output of an EMG sensor configured to generate a signal modulated with changes in muscle tone associated with autonomic arousal events.
 6. A method for monitoring a patient therapy, comprising: sensing one or more physiological conditions modulated by a patient's autonomic arousal response; detecting autonomic arousal events occurring during sleep based on the one or more sensed physiological conditions, wherein at least one of sensing the physiological conditions and detecting the autonomic arousal events is performed at least in part implantably; and discriminating between autonomic arousal events associated with sleep disorder events and autonomic arousal events not associated with sleep disorder events; and monitoring a patient therapy based at, least in part, on the discrimination of the autonomic arousal events.
 7. The method according to claim 6, further comprising adjusting the patient therapy based, at least in part, on the detected autonomic arousal events.
 8. The method according to claim 6, wherein the patient therapy comprises a neural stimulation therapy.
 9. The method according to claim 6, wherein: sensing the one or more physiological conditions comprises sensing sympathetic nerve activity; and detecting the autonomic arousal events is based at least in part on the sensed sympathetic nerve activity.
 10. The method according to claim 6, wherein the patient therapy comprises a therapy for treating hypertension.
 11. The method according to claim 6, further comprising: determining a trend of the autonomic arousal events; and using the autonomic arousal event trend to monitoring the patient therapy.
 12. The method according to claim 6, wherein: sensing the one or more physiological conditions comprises sensing heart rate; and detecting the autonomic arousal events comprises: determining heart rate variability based on the sensed heart rate; and detecting one or more of the autonomic arousal events based at least in part on the heart rate variability.
 13. The method according to claim 6, wherein: sensing the one or more physiological conditions comprises sensing at least one physiological condition that is modulated contemporaneously with an occurrence of an autonomic arousal event; and detecting the autonomic arousal events comprises detecting the autonomic arousal events contemporaneously with modulation of the physiological condition.
 14. A medical system for monitoring a patient therapy comprising: one or more sensors configured to sense one or more physiological conditions associated with a patient's autonomic arousal response; an implantable arousal detector coupled to the one or more sensors, the arousal detector configured to detect autonomic arousal events based on the one or more physiological conditions; and a controller operatively coupled to the arousal detector, the controller configured to discriminate between autonomic arousal events associated with sleep disorder events and autonomic arousal events not associated with sleep disorder events, and to monitor the patient therapy based at, least in part, on the discriminated autonomic arousal events.
 15. The medical system of claim 14 further comprising: a therapy unit, operatively coupled to the controller, configured to adjust the patient therapy based, at least in part, on the discriminated autonomic arousal events.
 16. The medical system of claim 15, wherein the therapy unit is configured to deliver a neurostimulation therapy to the patient, and is further configured to adjust the neurostimulation therapy based, at least in part, on the discriminated autonomic arousal events.
 17. The medical system of claim 15, wherein the therapy unit is configured to deliver a cardiac electrical stimulation therapy to the patient, and is further configured to adjust the cardiac electrical stimulation therapy based, at least in part, on the discriminated autonomic arousal events.
 18. The medical system of claim 15, wherein the therapy unit is configured to deliver a therapy to treat hypertension in the patient, and is further configured to adjust the therapy based, at least in part, on the discriminated autonomic arousal events.
 19. The medical system of claim 14, wherein the controller is configured to determine a trend of the detected autonomic arousal events, and to use the autonomic arousal event trend to monitoring the patient therapy.
 20. The medical system of claim 14, wherein the controller is configured to determine an arousal event index based on the detected autonomic arousal events, and to monitor the patient therapy based on the index. 